T cells can be activated by an antigen presenting cell. An activated T cell can bind to a cell that presents an antigen to which the T cell was activated via an interaction between a T cell receptor and major histocompatibility complex, and the activated T cell can kill the cell to which it is bound. It is possible to activate T cells from a donor against cells from a patient and generate cytotoxic T cells that kill patient cells. Such T cells are referred to as “alloreactive” T cells as they are activated from donor cells and are active against the major histocompatibility complex (MHC) antigens (sometimes identified as human leukocyte antigens or HLA) present on patient cells.
Alloreactive cytotoxic T cells can be prepared by isolating blood from a patient, separating white blood cells, and inactivating them. These inactivated patient cells can be mixed with white blood cells from a donor in a one-way mixed lymphocyte reaction. In the lymphocyte reaction, T cells among the donor cell population are activated against antigens presented by cells in the patient population, and activated cytotoxic T cells are generated against the patient cells. The activated cytotoxic T cells can be collected and administered to the patient. Cells in the patient, such as cancer cells, that display antigens recognized by the cytotoxic T cells will be killed.
HLAMatchmaker (HLAMm) is an algorithm used in the transplantation setting to predict alloantibody responses. HLAMm operates by finding permissible mismatches between molecularly HLA-type donors and recipients such to minimize rejection. When HLAMm is applied to the diverse HLA repertoire, it is able to predict B cell driven alloantibody generation following organ transplantation. However, the current algorithm has does not as reliably predict the T cell induced graft-versus host (GVH) disease.